KR20170032802A - Soluble microneedle patch for delivery of anti-acne drug - Google Patents

Abstract

The present invention relates to a skin administration system of an acne therapeutic agent, which stably impregnates an acne therapeutic agent and effectively delivers the same into the skin, thereby being able to exert an excellent effect. In addition, the skin administration system of an acne therapeutic agent is a microneedle including the acne therapeutic agent.

Description

[0002] Soluble microneedle patches for delivery of anti-acne medicines [

The present invention relates to a microneedle and a microneedle patch.

In general, microneedle is used for delivery of an active substance such as a drug in vivo, detection of an analyte in the body, and biopsy. The delivery of the pharmacologically or cosmetically active ingredient using microneedles is intended for the delivery of the active substance through the skin, not the vascular system such as blood vessels or lymphatic vessels.

Examples of the method using the microneedle include a method of forming a predetermined number of holes or more on the skin using a microneedle device such as a roller with a microneedle attached thereto, (Active ingredient) is coated on the skin to allow the active ingredient to be administered simultaneously with the perforation of the skin.

Acne, on the other hand, is an inflammatory skin disease in which hair follicles (open and closed), pimples, deep boils (cysts or tubercles) are formed in the face, neck, chest, back and shoulder. Acne usually occurs in the early teenage years, but symptoms can be severe around the age of 20, and can occur in adults in their 30s and 40s. Generally, even without treatment, acne usually disappears in a few years, but if left untreated, permanent scarring can be left. Therefore, it is important to treat properly at an early stage.

In the case of medicines such as adapalene, azelaic acid, and resorcinol, which are acne remedies, many studies have shown the effect on skin acne treatment, but the lack of skin-affinity (lipophilicity) So that permeation of the skin is not easy.

Therefore, there is a need for new methods that can be used to overcome the limitations of effective substance transfer due to skin barrier and improve the skin permeation efficiency in the application of acne remedy.

Korean Patent Publication No. 10-2014-0125364

A problem to be solved by the present invention is to provide a system for effectively delivering an acne treatment agent into the skin by stably impregnating an acne remedy with a soluble micro-needle, and a method for producing such a system.

Accordingly, the present invention provides a soluble micro-needle comprising an acne treatment agent.

The present invention also provides a microneedle patch comprising the microneedles.

The present invention also provides a method for producing a microneedle comprising an acne treatment agent.

In order to solve the above-mentioned problems, the present invention provides a soluble micro-needle comprising an acne treatment agent, and more preferably, the material forming the micro-needle is dissolved in the skin, and when the skin of the micro- The collapse causes the acne remedy to be released into the skin.

The inventors of the present invention have found that the acne treatment agent can be effectively delivered into the skin by impregnating the acne treatment agent in the soluble fine needle at the end of a long period of research and it is not easy to control the application amount of the conventional ointment or cream formulation, It is limited to be included in general cosmetics and / or ointment formulations, and the problems such as deterioration of acne caused by contaminated hands upon ointment application are solved at the origin, thus completing the present invention.

As used herein, the term "acne remedy" includes all substances and / or products used in the treatment of acne and is not limited to any substance and / or product exhibiting an acne treatment effect. Therefore, it can be used for oral administration, skin application, and the like.

As the acne remedy that can be used in the present invention, it may preferably be a retinoid compound, and the retinoid may be any natural and / or synthetic analogue of retinol-like compounds having biological activity of vitamin A or vitamin A in the skin, Geometric isomers and stereoisomers. The retinoids are preferably retinol, retinol esters (e.g., C ₂ -C ₂₂ alkyl esters of retinol, including retinyl palmitate, retinyl acetate, retinyl propionate), retinol aldehyde, retinal, Carotene and / or retinoic acid (all-transretenoic acid and / or 13-cis-retinoic acid), more preferably retinol ester. Among these compounds, adapalene {6- [3- (1-adamantyl) -4-methoxyphenyl] -2-naphthoic acid}, tocopheryl-retinoate [tocopherol ester (trans- or cis- And tazarotene (ethyl 6- [2- (4,4-dimethylthiochroman-6-yl) -ethynyl] nicotinate) can be preferably used.

In particular, in the present invention, adapalene can be used, among the acne treatment agents, by confirming a remarkable effect by using adapalene.

The present inventors have studied various administration systems, and no system is similar to the method of impregnating the dissolvable microneedles of the acne treatment agent. The inventors of the present invention have surprisingly invented that, after various efforts, impregnating micro-needles with acne treatment agent to solve the problem of skin permeability of acne treatment agent and to confirm a remarkable effect without side effects. In addition, by using the microneedles according to the present invention, non-skilled people can easily apply acne treatment without side effects by a noninvasive method, and it is possible to relieve the itching by the constant pain generated by applying the microneedles And the contained (dispersed) acne remedy can immediately exert its effect in the skin and exert excellent acne treatment and / or relieving effect.

As used herein, the term "impregnation" may refer to a form in which an acne remedy can be contained in a microneedle, preferably i) an acne treatment agent together with a solubilizing substance that forms a microneedle Or ii) a micro-needle may be punctured to contain an acne remedy in the pore. When the microneedles are prepared in the form of i) and ii), the acne remedy can effectively penetrate into the skin, and in particular, when microneedles are produced in the form of i), the problem of low skin permeability of the acne remedy Can be solved and the acne remedy can be stably impregnated in the formulation.

Therefore, it is most preferable that the substance which forms the microneedles is dissolved in the living body so that the acne remedy contained in the microneedles is effectively released into the skin.

In a preferred embodiment of the present invention, the material forming the microneedle is dissolved in the skin, and when the microneedles are applied to the skin, the microneedles are dissolved or collapsed, so that the acne treatment agent contained in the microneedles effectively penetrates into the skin Since the microneedles contain a soluble polymer, it is possible to reduce the number of application times and to maximize the effect of the acne treatment agent by releasing a small amount of the acne treatment agent in the skin to maintain the effect for a long time. In particular, the microneedles may contain a sustained-release polymer in order to release a small amount of the acne remedy in the skin. The sustained-release polymer may include, but is not limited to, poly (lactide), poly (glycolide), poly (lactide-co-glycolide), polyanhydride, polyorthoester, polyetherester , Biodegradable polymers such as polycaprolactone, polyester amide, poly (butyric acid), poly (valeric acid), polyurethane and copolymers thereof. Particularly, the release behavior can be controlled by changing the decomposition rate of the polymer according to the control of the fraction or the molecular weight of the copolymer material during the copolymerization.

In the present invention, the microneedles are preferably soluble in the skin. For example, hyaluronic acid, sodium carboxymethyl cellulose (Na-CMC), or the like may be used to form a soluble microneedle. , Water-soluble polymers such as vinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, and polyvinyl pyrrolidone; Sugars such as Xylose, Sucrose, Maltose, Lactose and Trehalose; Or a mixture thereof may be used. Considering the skin penetration strength of the micro-needle and the dissolution rate in the skin in general, it is preferable to use hyaluronic acid, sodium carboxymethyl cellulose (Na-CMC), and saccharide (Trehalose) is preferable, and it is more preferable to mix glycerin.

Preferably, the microneedles of the present invention may further include plasticizers, surfactants, preservatives, anti-inflammatory agents, etc. in addition to the above-mentioned components for forming microneedles.

Examples of the plasticizer include polyols such as ethylene glycol, propylene glycol, dipropylene glycols, butylene glycol, and glycerin. Or may be used in combination.

The length of the microneedles according to the present invention is not limited to a specific size.

In the present invention, the acne remedy may be included in an amount of 0.001 to 10% by weight, preferably 0.01 to 5% by weight, more preferably 0.1 to 1% by weight, based on the total weight of the microneedles. If it is contained in an amount of less than 0.001% by weight, it may not exhibit an effective effect, and if it is contained in an amount exceeding 10% by weight, the physical properties and durability of the fine needle may be affected.

When the microneedles according to the present invention are applied to the skin, the skin permeation amount can be remarkably improved as compared with the conventional skin administration systems.

The present invention also provides a microneedle patch comprising the microneedles, that is, a microneedle patch for administration (or delivery) of an acne treatment agent to which the microneedles are attached.

In the present invention, the patch may refer to a sheet having one or more micro-needles impregnated with the acne treatment agent of the present invention and having a surface with the micro-needle attached thereto. The size of the sheet is not limited to a specific size, but can be appropriately adjusted depending on the amount of the acne remedy to be absorbed into the skin or the attachment site. In addition, one or more, preferably a plurality of micro-needles may be attached to the surface of the sheet which can be attached to the skin.

In addition, it is possible to add an antiseptic agent to the surface of the patch which can be adhered to the skin, so that the acne treatment agent can penetrate into the hole formed by the micro-needle. In order to achieve a superior skin administration effect, .

The present invention also relates to a method for preparing a microcapsule, comprising the steps of: S1) filling a mold with an acne treatment agent and a substance forming a microneedle including a skin-soluble substance; And S2) warming the mold, drying and then separating the mold.

The method may be prepared by impregnating a micro-needle with an acne remedy, and the impregnation may include, but is not limited to, i) containing an acne remedy together with a skin-soluble substance forming a microneedle, or ii) A hole in the needle to contain an acne remedy in the hole, and the like.

In the present invention, in order to impregnate the acne treatment agent into the microneedles, a substance for forming the microneedles and a therapeutic agent for acne are mixed together and filled into a mold for microneedle formation. The mold is heated, Needles can be made.

In the present invention, the in-skin solubility material may include, for example, hyaluronic acid, sodium carboxymethyl cellulose (Na-CMC), vinyl pyrrolidone-vinyl acetate copolymer, polyvinyl alcohol vinyl alcohol, and polyvinyl pyrrolidone; Sugars such as Xylose, Sucrose, Maltose, Lactose and Trehalose; Or a mixture thereof may be used.

The present invention provides a method for producing an acne treatment agent administration system capable of exhibiting an excellent effect through effective skin delivery of an acne treatment agent.

BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate exemplary embodiments of the invention and, together with the description of the invention, Should not be construed as limited.
FIG. 1 is a view showing one example of various methods for manufacturing a microneedle according to the present invention.
FIG. 2 shows a Franz diffusion cell for evaluating the drug release behavior of the microneedles according to the present invention.
3 is a graph showing skin permeation amount of adapalene of Example 1 and Comparative Example 1. Fig.

Hereinafter, embodiments of the present invention will be described in detail to facilitate understanding of the present invention. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.

≪ Preparation of soluble fine needle >

Soluble microneedles are prepared by solution casting method, and they are prepared by casting solution into mold, filling solution into micro mold by vacuum or centrifugation and drying.

Conventional synthetic and natural water-soluble polymers were used for the materials forming the microneedle structure.

≪ Preparation of soluble fine needle containing adapalene (Example 1) >

ingredient Example 1
(Unit: wt%) oligo-HA 6 Na-CMC 6 Trehalose 10 Glycerin 4 Dipropylene glycol 2.7 PEG-40 Hydrogenated Chain Oil One adapalene 0.3 water To 100

(Hyaluronic acid), Na-CMC (sodium carboxymethyl cellulose) and Trehalose were dissolved in purified water and then glycerin, PEG-40 hydrogenated castor oil (HCO-40) and adapalene solution 10%, dipropylene glycol 90%) to prepare adapalene - dispersed microneedle solution. The prepared solution was cast in a silicon microneedle mold and then centrifuged at 3000 rpm for 10 minutes to fill the micro mold with the solution. After the solution was filled, it was dried in a drying oven (70 ° C) for 3 hours, and the fine needle was separated from the silicone mold using an adhesive film (Example 1).

≪ Preparation of adapalene-containing cream (Comparative Example 1) >

ingredient Comparative Example 1
(Unit: wt%) C14-22 alcohol, C12-20 alkyl glucoside
(Mixture C14-22 alcohol: C12-20 alkyl glucoside = 80:20 weight ratio) 1.5 Glyceryl stearate, phage-100 stearate
(Mixture 50:50 weight ratio) 1.2 Glyceryl stearate 0.9 Cetearyl alcohol 1.5 Polyglyceryl-3 methyl glucoside distearate 1.5 Hydrogenated polydecene 4.5 Cyclohexasiloxane 3.5 Carbomer 0.2 Tromethamine 0.2 glycerin 3 Dipropylene glycol 5 1,2-hexanediol 2 adapalene One Purified water To 100

In order to compare the effect of the active ingredient applied to the microneedle-impregnated active ingredient and the underwater emulsifier type cream, a cream containing adapalene in the composition of Table 2 was prepared (Comparative Example 1).

<Experimental Example 1>

Drug release behavior

The present inventors measured the adapalene content of porcine skin tissue and acceptor solution with Franz diffusion cell using liquid chromatography (Liquid Chromatography) over time. Example 1 was applied to pig skin and Comparative Example 1 was applied to penetrate into pig skin and dissolve, followed by removal of fine needle and cream.

Adapalene-absorbed pig skin was loaded into a franz diffusion cell according to Example 1 and Comparative Example 1 (Fig. 2), and skin permeation amount of adapalene with time was compared.

As a result, as shown in FIG. 3, in Comparative Example 1, the amount of permeation through the skin was about 1.6 μg, which was insignificant. However, the adapalene impregnated in the micro needle was directly penetrated to the skin by the needle, Or more than 10 times higher than cream.

Claims (9)

Soluble microneedles containing acne remedy. The method according to claim 1,
Wherein the material forming the microneedle is dissolved in the skin. 3. The method of claim 2,
The microneedle forming material may be selected from the group consisting of hyaluronic acid, sodium-carboxymethylcellulose, sodium carboxymethyl cellulose (Na-CMC), vinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohol Poly vinyl alcohol, polyvinyl pyrrolidone, saccharides, or a mixture of two or more thereof. The method of claim 3,
Wherein the microneedles further comprise a plasticizer in addition to the material forming the microneedles. The method according to claim 1,
Wherein the acne treatment agent is adapalene. The method according to claim 1,
Wherein the acne treatment agent is contained in an amount of 0.001 to 10% by weight based on the total weight of the microneedles. The method according to claim 1,
Wherein the microneedles improve the skin permeation rate of the acne treatment agent. A microneedle patch comprising a microneedle according to any one of claims 1 to 7. S1) filling a mold with a substance to form a micro-needle including an acne remedy and an intracutaneous solubility material; And
S2) warming the mold, drying and then separating the mold.

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